Non-arteritic branch/central retinal artery occlusions (BRAO/CRAO) and amaurosis fugax (AF) are predominantly caused by embolism. Additionally, transported embolic material could cause ischemic ...stroke. The aim of the study was to investigate the prevalence, pattern and underlying cause of concurrent acute brain infarctions in unselected patients with RAO and AF.
A total of 213 consecutive patients with BRAO (20.7%), CRAO (47.4%), or AF (31.9%) were retrospectively studied from 2008 to 2013. Magnetic resonance imaging (MRI) was used to detect acute brain infarctions and a cardiovascular workup was performed to detect underlying etiologies according to the Trial of Org 10172 in Acute Stroke Management (TOAST).
MRI was obtained after 23.78 (±32.26) hours from the time of symptom onset. Acute brain infarctions were detected in 49 patients (23%); 44 of them (89.8%) did not experience any additional neurological symptoms. Older age (p < 0.001/p < 0.001), hypertension (p = 0.01/p = 0.03), atrial fibrillation (p = 0.006/p = 0.03) and type of RAO (p = 0.02/p = 0.016) were associated with total/silent stroke, respectively. In multivariate analysis, only age and type of occlusion remained positive predictors for silent stroke. Etiology of BRAO/CRAO and AF remained undetermined in 124 patients (58.2%). This rate was lower in patients with acute stroke (40.8 vs. 63.4%).
Silent brain infarction is a frequent finding in unselected patients with BRAO/CRAO and AF. Etiology remains undetermined in approximately every second case. Because silent brain infarctions bear a high risk of future stroke, patients with BRAO/CRAO and AF should undergo prompt neuroimaging and cardiovascular checkup, preferably on a stroke unit.
We aimed to assess the prognostic value of serum β-synuclein (β-syn), neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in patients with moderate-to-severe acute ischemic ...stroke. We measured β-syn, GFAP and NfL in serum samples collected one day after admission in 30 adult patients with moderate-to-severe ischemic stroke due to middle cerebral artery (MCA) occlusion. We tested the associations between biomarker levels and clinical and radiological scores (National Institute of Health Stroke Scale scores, NIHSS, and Alberta Stroke Program Early CT Score, ASPECTS), as well as measures of functional outcome (modified Rankin Scale, mRS). Serum biomarkers were significantly associated with ASPECTS values (β-syn p = 0.0011, GFAP p = 0.0002) but not with NIHSS scores at admission. Patients who received mechanical thrombectomy and intravenous thrombolysis showed lower β-syn (p = 0.029) und NfL concentrations (p = 0.0024) compared to patients who received only mechanical thrombectomy. According to median biomarker levels, patients with high β-syn, NfL or GFAP levels showed, after therapy, lower clinical improvement (i.e., lower 24-h NIHSS change), higher NIHSS scores during hospitalization and higher mRS scores at 3-month follow-up. Elevated serum concentrations of β-syn (p = 0.016), NfL (p = 0.020) or GFAP (p = 0.010) were significantly associated with 3-month mRS of 3-6 vs. 0-2 even after accounting for age, sex and renal function. In patients with moderate-to-severe acute ischemic stroke, serum β-syn, NfL and GFAP levels associated with clinical and radiological scores at different timepoints and were able to predict short- and middle-term clinical outcomes.
Abstract
Background
Neurologic manifestations are increasingly reported in patients with coronavirus disease 2019 (COVID-19). Yet, data on prevalence, predictors and relevance for outcome of ...neurological manifestations in patients requiring intensive care are scarce. We aimed to characterize prevalence, risk factors and impact on outcome of neurologic manifestations in critically ill COVID-19 patients.
Methods
In the prospective, multicenter, observational registry study PANDEMIC (Pooled Analysis of Neurologic DisordErs Manifesting in Intensive care of COVID-19), we enrolled COVID-19 patients with neurologic manifestations admitted to 19 German intensive care units (ICU) between April 2020 and September 2021. We performed descriptive and explorative statistical analyses. Multivariable models were used to investigate factors associated with disorder categories and their underlying diagnoses as well as to identify predictors of outcome.
Results
Of the 392 patients included in the analysis, 70.7% (277/392) were male and the mean age was 65.3 (SD ± 3.1) years. During the study period, a total of 2681 patients with COVID-19 were treated at the ICUs of 15 participating centers. New neurologic disorders were identified in 350 patients, reported by these centers, suggesting a prevalence of COVID-19-associated neurologic disorders of 12.7% among COVID-19 ICU patients. Encephalopathy (46.2%; 181/392), cerebrovascular (41.0%; 161/392) and neuromuscular disorders (20.4%; 80/392) were the most frequent categories identified. Out of 35 cerebrospinal fluid analyses with reverse transcriptase PCR for SARS-COV-2, only 3 were positive. In-hospital mortality was 36.0% (140/389), and functional outcome (mRS 3 to 5) of surviving patients was poor at hospital discharge in 70.9% (161/227). Intracerebral hemorrhage (OR 6.2, 95% CI 2.5–14.9,
p
< 0.001) and acute ischemic stroke (OR 3.9, 95% CI 1.9–8.2,
p
< 0.001) were the strongest predictors of poor outcome among the included patients.
Conclusions
Based on this well-characterized COVID-19 ICU cohort, that comprised 12.7% of all severe ill COVID-19 patients, neurologic manifestations increase mortality and morbidity. Since no reliable evidence of direct viral affection of the nervous system by COVID-19 could be found, these neurologic manifestations may for a great part be indirect para- or postinfectious sequelae of the infection or severe critical illness. Neurologic ICU complications should be actively searched for and treated.
It remains unclear if principal components of the local cerebral stroke immune response can be reliably and reproducibly observed in patients with acute large-vessel-occlusion (LVO) stroke. We ...prospectively studied a large independent cohort of
= 318 consecutive LVO stroke patients undergoing mechanical thrombectomy during which cerebral blood samples from within the occluded anterior circulation and systemic control samples from the ipsilateral cervical internal carotid artery were obtained. An extensive protocol was applied to homogenize the patient cohort and to standardize the procedural steps of endovascular sample collection, sample processing, and laboratory analyses. N = 58 patients met all inclusion criteria. (1) Mean total leukocyte counts were significantly higher within the occluded ischemic cerebral vasculature (I) vs. intraindividual systemic controls (S): +9.6%, I: 8114/µL ± 529 vs. S: 7406/µL ± 468,
= 0.0125. (2) This increase was driven by neutrophils: +12.1%, I: 7197/µL ± 510 vs. S: 6420/µL ± 438,
= 0.0022. Leukocyte influx was associated with (3) reduced retrograde collateral flow (R
= 0.09696,
= 0.0373) and (4) greater infarct extent (R
= 0.08382,
= 0.032). Despite LVO, leukocytes invade the occluded territory via retrograde collateral pathways early during ischemia, likely compromising cerebral hemodynamics and tissue integrity. This inflammatory response can be reliably observed in human stroke by harvesting immune cells from the occluded cerebral vascular compartment.
Data on clinical long-term outcome after the acute phase of hypoglycemic encephalopathy (HE) using validated outcome scales is currently unavailable. Here we report the results of a systematic ...literature search for studies on HE and data on long-term outcome in patients with HE admitted to three Charité hospitals between January 2005 and July 2010. HE was defined as coma/stupor and blood glucose levels <50 mg/dl on admission, persistence of coma/stupor for ≥24 h despite normalization of blood glucose levels, and exclusion of any other cause of coma/stupor. Outcome was assessed using the modified Rankin scale (mRS), Glasgow Outcome Scale (GOS), and Barthel index (BI). Fifteen patients were included, with a mean age of 60 years (range 29–79). Two were lost to follow-up. Of the remaining 13 patients, six had died (46 %). In the seven survivors, the median mRS score was 0 (range 0–5), median GOS score was 5 (range 2–5), and median BI was 100 (range 0–100). MRIs made in the acute phase were available for three patients and revealed no obvious relation between lesion size or pattern and clinical outcome. To our knowledge, this is the first case series using validated clinical scoring systems to determine clinical long-term outcome after HE. The results suggest that mortality is high, but long-term survival with little or no disability is possible and can be observed in the majority of survivors. Risk of death or poor outcome does not seem to be related to MRI features in the acute phase but rather to other presumably medical factors.
At present, the flexible endoscopic evaluation of swallowing (FEES) is one of the most commonly used methods for the objective assessment of swallowing. This multicenter trial prospectively collected ...data on the safety of FEES and also assessed the impact of this procedure on clinical dysphagia management.
Patients were recruited in 23 hospitals in Germany and Switzerland from September 2014 to May 2017. Patient characteristics, professional affiliation of the FEES examiners (physicians or speech and language therapists), side-effects and cardiorespiratory parameters, severity of dysphagia and clinical consequences of FEES were documented.
2401 patients, mean age 69.8 (14.6) years, 42.3% women, were included in the FEES-registry. The most common main diagnosis was stroke (61%), followed by Parkinson's disease (6.5%). FEES was well tolerated by patients. Complications were reported in 2% of examinations, were all self-limited and resolved without sequelae and showed no correlation to the endoscopist's previous experience. In more than 50% of investigations FEES led to changes of feeding strategies, in the majority of cases an upgrade of oral diet was possible.
This study confirmed that FEES, even when performed by less experienced clinicians is a safe and well tolerated procedure and significantly impacts on the patients' clinical course. Implementation of a FEES-service in different clinical settings may improve dysphagia care.
ClinicalTrials.gov NCT03037762, registered January 31st 2017.
Mild cognitive impairment and dementia are common and serious co-morbidities in people with chronic heart failure (HF) as they increase hospitalization rates, mortality and health care costs. Upon ...other factors, dysregulated cerebral perfusion might contribute to brain pathology. We aimed to evaluate the association of non-invasively measured blood flow (BF) and pulsatility index (PI) of the internal carotid artery (ICA) with (i) chronic HF parameters, (ii) brain morphologic measures and (iii) cognitive impairment.
This post-hoc analysis of the observational, prospective Cognition.Matters-HF study included 107 chronic HF patients without atrial fibrillation or carotid artery stenosis (aged 63 ± 10 years; 19% women). Using extracranial sonography, we measured ICA-BF and ICA-PI 1.5 cm distal of the carotid bifurcation. Brain magnetic resonance imaging was performed on a 3-Tesla scanner to quantify cerebral atrophy, hippocampal atrophy and white matter hyperintensities. Extensive neuropsychological testing tested the cognitive domains intensity of attention, visual/verbal memory and executive function (including its subdomains selectivity of attention, visual/verbal fluency and working memory) using a comprehensive test battery. (i) Neither ICA-BF (median 630 (quartiles 570, 700) mL/min) nor ICA-PI (1.05 (0.96. 1.23)) related to left ventricular ejection fraction, left atrial volume index or NT-proBNP. (ii) Higher ICA-PI (r = 0.25; P = 0.011), but not ICA-BF (r = 0.08; P = 0.409), associated with increased volume of white matter hyperintensities beyond ageing, while neither ICA-PI nor ICA-BF related to cerebral or hippocampal atrophy indices. (iii) ICA-BF, but not ICA-PI, positively correlated with age-adjusted T-scores of executive function (r = 0.38; P < 0.001) and its subdomains working memory (r = 0.32; P < 0.001) and visual/verbal fluency (r = 0.32; P < 0.001). In a multivariate linear model of executive function, only ICA-BF (T = 3.79; P < 0.001), but not HF or magnetic resonance imaging parameters, remained a significant correlate of executive function.
ICA-BF and ICA-PI, measured in broadly available extracranial sonography, independently related to measures of functional and structural brain changes in people with chronic HF, respectively. Due to limitations of this cross-sectional approach without a healthy control group, larger controlled longitudinal studies are needed to further elucidate the role of ICA-BF dysregulation and its implication for clinical care in this vulnerable cohort.
The syndrome of pathological laughing and crying (PLC) is characterized by episodes of involuntary outbursts of emotional expression. Although this phenomenon has been referred to for over a century, ...a clear-cut clinical definition is still lacking, and underlying pathophysiological mechanisms are not well understood. In particular, it remains ill-defined which kind of stimuli—contextually appropriate or inappropriate—elicit episodes of PLC, and if the phenomenon is a result of a lack of inhibition from the frontal cortex (“top-down-theory”) or due to an altered processing of sensory inputs at the brainstem level (“bottom-up-theory”). To address these questions, we studied ten amyotrophic lateral sclerosis (ALS) patients with PLC and ten controls matched for age, sex and education. Subjects were simultaneously exposed to either emotionally congruent or incongruent visual and auditory stimuli and were asked to rate pictures according to their emotional quality. Changes in physiological parameters (heart rate, galvanic skin response, activity of facial muscles) were recorded, and a standardized self-assessment lability score (CNS-LS) was determined. Patients were influenced in their rating behaviour in a negative direction by mood-incongruent music. Compared to controls, they were influenced by negative stimuli, i.e. they rated neutral pictures more negatively when listening to sad music. Patients rated significantly higher on the CNS-LS. In patients, changes of electromyographic activity of mimic muscles during different emotion-eliciting conditions were explained by frontal cortex dysfunction. We conclude that PLC is associated with altered emotional suggestibility and that it is preferentially elicited by mood-incongruent stimuli. In addition, physiological reactions as well as behavioural changes suggest that this phenomenon is primarily an expression of reduced inhibitory activity of the frontal cortex, since frontal dysfunction could explain changes in physiological parameters in the patient group. We consider these findings being important for the clinical interpretation of emotional reactions of ALS patients.
Moderate hypothermia after decompressive surgery might not be beneficial for stroke patients. However, normothermia may prove to be an effective method of enhancing neurological outcomes. The study ...aims were to evaluate the application of a pre-specified normothermia protocol in stroke patients after decompressive surgery and its impact on temperature load, and to describe the functional outcome of patients at 12 months after treatment.
We analysed patients with space-occupying middle cerebral artery (MCA) infarction treated with decompressive surgery and a pre-specified temperature management protocol. Patients treated primarily with device-controlled normothermia or hypothermia were excluded. The individual temperature load above 36.5 °C was calculated for the first 96 h after hemicraniectomy as the Area Under the Curve, using °C x hours. The effect of temperature load on functional outcome at 12 months was analysed by logistic regression.
We included 40 stroke patients treated with decompressive surgery (mean SD age: 58.9 10.1 years; mean SD time to surgery: 30.5 16.7 hours). Fever (temperature > 37.5 °C) developed in 26 patients during the first 96 h after surgery and mean (SD) temperature load above 36.5 °C in this time period was 62,3 (+/- 47,6) °C*hours. At one year after stroke onset, a moderate to moderately severe disability (modified Rankin Scale score of 3 or 4) was observed in 32% of patients, and a severe disability (score of 5) in 37% of patients, respectively. The lethality in the cohort at 12 months was 32%. The temperature load during the first 96 h was not an independent predictor for 12 month lethality (OR 0.986 95%-CI:0.967-1.002; p < 0.12).
Temperature control in surgically treated patients with space-occupying MCA infarction using a pre-specified protocol excluding temperature management systems resulted in mild hyperthermia between 36.8 °C and 37.2 °C and a low overall temperature load. Future prospective studies on larger cohorts comparing different strategies for normothermia treatment including temperature management devices are needed.
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